5W5D

Crystal structure of the primed SNARE-Complexin-Synaptotagmin-1 C2B complex

Summary for 5W5D

• Entry DOI: 10.2210/pdb5w5d/pdb
• Descriptor: Vesicle-associated membrane protein 2, Syntaxin-1A, Synaptosomal-associated protein 25, ... (8 entities in total)
• Functional Keywords: prefusion primed complex, neuronal exocytosis, synaptotagmin, snare complex, complexin, synchronous neurotransmitter release, exocytosis
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type IV membrane protein: P63045 P32851; Cytoplasm, perinuclear region : P60881 P60881; Cytoplasm, cytosol : P63041; Cytoplasmic vesicle, secretory vesicle membrane ; Single-pass membrane protein : P21707
• Total number of polymer chains: 6
• Total formula weight: 56033.07

Authors

Zhou, Q.,Brunger, A.T. (deposition date: 2017-06-14, release date: 2017-08-23, Last modification date: 2023-10-04)

Primary citation

Zhou, Q.,Zhou, P.,Wang, A.L.,Wu, D.,Zhao, M.,Sudhof, T.C.,Brunger, A.T.
The primed SNARE-complexin-synaptotagmin complex for neuronal exocytosis.
Nature, 548:420-425, 2017

PubMed Abstract: Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE-complexin-synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for the primed pre-fusion state. Ca binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. The tripartite SNARE-complexin-synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.

PubMed: 28813412
DOI: 10.1038/nature23484

Experimental method

X-RAY DIFFRACTION (2.496 Å)